title: An interleukin-10 gene polymorphism associated with the development of cervical lesions in women infected with Human Papillomavirus and using oral contraceptives.
abstract: Human Papillomavirus (HPV) infection plays a crucial role in the development of cervical lesions and tumors, however most lesions containing high-risk HPVs do not progress to cervical tumors. Some studies suggest that the use of oral contraceptives may increase the risk of cervical carcinogenesis, but this has not been confirmed by all the studies. Cytokines are important molecules that act in the defense of an organism against viral infections. Several genetic studies have attempted to correlate cytokine polymorphisms with human diseases, including cancer. The significance of IL10 polymorphisms for cancer is that they have both immunosuppressive and antiangiogenic properties. We aimed to investigate the role of promoter polymorphisms in the IL10 gene in women with cervical lesions associated with HPV infection, in the presence of the use of oral contraceptives. Using High Resolution Melt analysis (HRM), we analyzed an SNP -1082A/G and -819C/T in interleukin-10 promoter region in 364 Brazilian women: 171 with cervical lesions and HPV infection, and 193 with normal cytological results and HPV-negative. We observed no significant differences in genotype and allele frequencies in the two loci between patients and healthy controls. Furthermore, in the haplotype analysis of IL10, we found that CA haplotype was significantly more frequent in patients infected with HPV than in the control group (p = 0.0188). We did not find any genotype and allelic association of the IL10 gene polymorphisms between cases and controls. However, in this study, when the HPV-positive patients were stratified according to their use of contraceptives, we found a significant association between the -1082G allele (p = 0.0162) and -1082GG genotype (p = 0.0332) among HPV-infected patients who used oral contraceptives. Our findings suggest that -1082A/G gene polymorphism represents a greater susceptibility to progressive cervical lesions in HPV- infected women who use oral contraceptives.
authors.affiliation: Laboratory of Molecular Studies and Experimental Therapy, Department of Genetics, Federal University of Pernambuco, Pernambuco, Brazil. Electronic address: babisimas@gmail.com.
authors.forename: Bárbara Simas
authors.initials: BS
authors.lastname: Chagas
authors.forename: Ana Pavla Almeida Diniz
authors.initials: AP
authors.lastname: Gurgel
authors.forename: Heidi Lacerda Alves
authors.initials: HL
authors.lastname: da Cruz
authors.forename: Carolina Maria Medeiros
authors.initials: CM
authors.lastname: Amaral
authors.forename: Marcus Vinicius
authors.initials: MV
authors.lastname: Cardoso
authors.forename: Jacinto da Costa
authors.initials: Jda C
authors.lastname: Silva Neto
authors.forename: Luiz Antônio Ferreira
authors.initials: LA
authors.lastname: da Silva
authors.forename: Eugênia Maria Bezerra
authors.initials: EM
authors.lastname: de Albuquerque
authors.forename: Maria Tereza Cartaxo
authors.initials: MT
authors.lastname: Muniz
authors.forename: Antonio Carlos
authors.initials: AC
authors.lastname: de Freitas
mesh_terms: D000328:Adult; D003276:Contraceptives, Oral; D005260:Female; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics*; D008875:Middle Aged; D030361:Papillomavirus Infections / Q000150:complications* / Q000453:epidemiology*; D020641:Polymorphism, Single Nucleotide; D002583:Uterine Cervical Neoplasms / Q000150:complications / Q000453:epidemiology / Q000235:genetics*; D055815:Young Adult
chemical_list: D003276:Contraceptives, Oral; D016753:Interleukin-10
keywords: Cervical cancer; Contraceptive; High resolution melting; Human Papillomavirus (HPV); Interleukin-10